UMMS Affiliation

Department of Medicine, Division of Gastroenterology

Publication Date

2019-02-05

Document Type

Article

Disciplines

Digestive System | Endocrine System Diseases | Endocrinology | Hormones, Hormone Substitutes, and Hormone Antagonists | Nutritional and Metabolic Diseases | Surgical Procedures, Operative

Abstract

Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut and is a key driver of enhanced insulin secretion.

Keywords

GLP-1, bariatric surgery, enteroendocrine cells, gut hormones, intestinal transit, mass spectrometry, peptidomics, transcriptomics

Rights and Permissions

Copyright 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

DOI of Published Version

10.1016/j.celrep.2019.01.047

Source

Cell Rep. 2019 Feb 5;26(6):1399-1408.e6. doi: 10.1016/j.celrep.2019.01.047. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID

30726726

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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